Assessment of cerebral spinal fluid biomarkers and microRNA-mediated disease mechanisms in spinal muscular atrophy patient samples

Cerebral spinal fluid (CSF) is a promising biospecimen for the detection of central nervous system biomarkers to monitor therapeutic efficacy at the cellular level in neurological diseases. Spinal muscular atrophy (SMA) patients receiving intrathecal antisense oligonucleotide (nusinersen) therapy tend to show improved motor function, but the treatment effect on cellular health remains unknown. The objective of this study was to assess the potential of extracellular RNAs and microRNAs, including the astrocyte-secreted microRNA miR-146a, in SMA patient CSF as indicators of neuron and glial health following nusinersen treatment.We then used mRNA sequencing and multi-electrode arrays to assess the transcriptional and functional effects of miR-146a on healthy and SMA induced pluripotent stem cell-derived motor neurons.